rs17136053

Variant names:

• chr16-2763176-C-G
• rs17136053
• NM_016333.4:c.2648C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-2763176-C-G
• chr16-2763176-C-A
• chr16-2763176-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016333.4(SRRM2):​c.2648C>G​(p.Ser883Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,054 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (164 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (143 hom.)
• Consequence: SRRM2 NM_016333.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.06
• Publications: 8 publications found

Genes affected

SRRM2 (HGNC:16639): (serine/arginine repetitive matrix 2) Enables C2H2 zinc finger domain binding activity and protein N-terminus binding activity. Involved in mRNA splicing, via spliceosome. Located in Cajal body and nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Biomarker of Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

SRRM2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal dominant 72

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016534626).
• BP6: Variant 16-2763176-C-G is Benign according to our data. Variant chr16-2763176-C-G is described in ClinVar as Benign. ClinVar VariationId is 720836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016333.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM2	NM_016333.4	MANE Select	c.2648C>G	p.Ser883Cys	missense	Exon 11 of 15	NP_057417.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM2	ENST00000301740.13	TSL:1 MANE Select	c.2648C>G	p.Ser883Cys	missense	Exon 11 of 15	ENSP00000301740.8	Q9UQ35-1
	SRRM2	ENST00000576924.6	TSL:1	c.2648C>G	p.Ser883Cys	missense	Exon 11 of 15	ENSP00000461181.2	Q9UQ35-1
	SRRM2	ENST00000571378.5	TSL:1	c.2360C>G	p.Ser787Cys	missense	Exon 10 of 10	ENSP00000458647.1	I3L182

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3760 AN: 152092 Hom.: 164 Cov.: 31

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00637 AC: 1600 AN: 251356 AF XY: 0.00436

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.00388

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00251 AC: 3662 AN: 1461844 Hom.: 143 Cov.: 83 AF XY: 0.00207 AC XY: 1504 AN XY: 727230

African (AFR) AF: 0.0907 AC: 3036 AN: 33478

American (AMR) AF: 0.00461 AC: 206 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00589 AC: 34 AN: 5768

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1112004

Other (OTH) AF: 0.00513 AC: 310 AN: 60396

GnomAD4 genome AF: 0.0247 AC: 3764 AN: 152210 Hom.: 164 Cov.: 31 AF XY: 0.0237 AC XY: 1763 AN XY: 74442

African (AFR) AF: 0.0863 AC: 3583 AN: 41498

American (AMR) AF: 0.00765 AC: 117 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68004

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.00132 Hom.: 3

Bravo AF: 0.0283

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0848 AC: 373

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00784 AC: 952

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.071
Sift4G	Pathogenic	0.0010	D
Polyphen		0.0020	B
Vest4		0.23
MVP		0.38
ClinPred		0.021	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.56
gMVP		0.27
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17136053; hg19: chr16-2813177;